Professor David Baker BSc PhD
About David Baker
Malaria Centre Head of Biology
- David Baker's Contacts
- Room 314b
- Keppel Street
- WC1E 7HT
- T: +44 (0) 20 7927 2664
David completed his PhD in 1988 at the University of Hull on the molecular biology of the intestinal parasite Giardia lamblia. He then moved to the London School of Hygiene & Tropical Medicine to work on the sexual stages of the malaria parasite Plasmodium falciparum. Current research is focused on investigating signal transduction pathways that regulate development of the most serious human malaria parasite Plasmodium falciparum. David is also involved in drug discovery work to exploit knowledge generated on these pathways to develop new antimalarial drugs.
I am involved in various aspects of teaching the MSc in Molecular Biology of Infectious Diseases (MBID). I organise the D2 Module - Molecular Biology: Research Progress and Applications (3160).
David Baker’s research group uses biochemical and genetic approaches to study the cyclic nucleotide signal transduction pathways of malaria parasites. The cyclic nucleotides cAMP and cGMP perform a whole spectrum of cellular functions in diverse organisms. Earlier work from other laboratories suggested that both of these second messenger molecules may play roles in malaria parasite differentiation. Our studies have focused on the cyclase enzymes that synthesise cyclic nucleotides, the phosphodiesterases that degrade them, but also on the protein kinase that is activated by cGMP (PKG). We have found that in Plasmodium falciparum cGMP and PKG play an essential role in triggering the formation (gametogenesis) of mature sexual parasite forms which are required to transmit disease to the mosquito vector. As part of a collaboration we also showed that this pathway is important for the development of the ookinete form of P. berghei within the mosquito. It is now becoming clear that cGMP signalling and the PKG enzyme are vital for multiple parasite stages, because using specific PKG inhibitors in conjunction with inhibitor-insensitive transgenic parasites we have demonstrated that asexual blood stage schizogony cannot progress if this kinase is blocked. Recently, with others we have shown that PKG functions upstream of a protease cascade and a calcium-dependent protein kinase (CDPK5) that are also required for asexual blood stage schizont rupture and merozoite egress. Since drug resistance is a huge problem, we are investigating whether cyclic nucleotide signalling pathways could be targeted in the development of novel antimalarial drugs. He became an Affiliated member of the EVIMalaR European Network of Excellence (www.evimalar.org) in 2010.
David received a Wellcome Trust Senior Investigator Award in 2015. This is a joint award with Professor Mike Blackman at the MRC National Institute for Medical Research that will focus on the cGMP signalling pathway in malaria parasites.
- Drug discovery and development
- Cell biology
- Molecular biology
Disease and Health Conditions
- Infectious disease
- Antiprotozoal Drug Discovery
- Artemisinin Resistance
- Cell Signalling
- Drug Efficacy
- Gene Expression
- Infectious Diseases
- Microbial Pathogenicity
- Plasmodium Falciparum Gametocyte Biology
- Wellcome Trust
- cGMP-dependent Protein Kinase
- cell biology
- drug development
- molecualr biology
- structural biology
Crystal Structures of the Carboxyl cGMP Binding Domain of the Plasmodium falciparum cGMP-dependent Protein Kinase Reveal a Novel Capping Triad Crucial for Merozoite Egress.
Kim, J.J. ; Flueck, C. ; Franz, E. ; Sanabria-Figueroa, E. ; Thompson, E. ; Lorenz, R. ; Bertinetti, D. ; Baker, D.A. ; Herberg, F.W. ; Kim, C. ;
PLoS Pathog, 2015; 11(2):e1004639
The mu-subunit of Plasmodium falciparum clathrin-associated adaptor protein 2 modulates in vitro parasite response to artemisinin and quinine.
Henriques, G. ; van Schalkwyk, D.A. ; Burrow, R. ; Warhurst, D.C. ; Thompson, E. ; Baker, D.A. ; Fidock, D.A. ; Hallett, R. ; Flueck, C. ; Sutherland, C.J. ;
Antimicrob Agents Chemother, 2015;
A transcriptional switch underlies commitment tosexual development in malaria parasites
Kafsack, B.F.; Rovira-Graells, N.; Clark, T.G.; Bancells, C.; Crowley, V.M.; Campino, S.G.; Williams, A.E.; Drought, L.G.; Kwiatkowski, D.P.; Baker, D.A.; Cortés, A.; Llinás, M.;
Nature, 2014; 507(7491):248-52
Phosphoinositide Metabolism Links cGMP-Dependent Protein Kinase G to Essential Ca2+ Signals at Key Decision Points in the Life Cycle of Malaria Parasites.
Brochet, M. ; Collins, M.O. ; Smith, T.K. ; Thompson, E. ; Sebastian, S. ; Volkmann, K. ; Schwach, F. ; Chappell, L. ; Gomes, A.R. ; Berriman, M. ; Rayner, J.C. ; Baker, D.A. ; Choudhary, J. ; Billker, O. ;
PLoS Biol, 2014; 12(3):e1001806
Malaria Parasite cGMP-dependent Protein Kinase Regulates Blood Stage Merozoite Secretory Organelle Discharge and Egress
Collins, C. R.; Hackett, F.; Strath, M.; Penzo, M.; Withers-Martinez, C.; Baker, D. A.; Blackman, M. J.
Plos Pathogens, 2013; 9(5)
A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes.
Dvorin, J.D.; Martyn, D.C.; Patel, S.D.; Grimley, J.S.; Collins, C.R.; Hopp, C.S.; Bright, A.T.; Westenberger, S.; Winzeler, E.; Blackman, M.J.; Baker, D.A.; Wandless, T.J.; Duraisingh, M.T.;
Science, 2010; 328(5980):910-2
A cyclic GMP signalling module that regulates gliding motility in a malaria parasite
Moon, R.W.; Taylor, C.J.; Bex, C.; Schepers, R.; Goulding, D.; Janse, C.J.; Waters, A.P.; Baker, D.A.; Billker, O.
PLoS Pathog, 2009; 5(9):e1000599
Gametogenesis in Malaria Parasites Is Mediated by the cGMP-Dependent Protein Kinase.
McRobert, L.; Taylor, C.J.; Deng, W.; Fivelman, Q.L.; Cummings, R.M.; Polley, S.D.; Billker, O.; Baker, D.A.;
PLoS Biol, 2008; 6(6):e139
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